Objective To analyze risk factors for severe and critically severe (hereinafter referred to as critical) coronavirus disease 2019 (COVID-19) combined with multidrug-resistant organism(MDRO) infection. Methods Clinical data of critical COVID-19 patients in the intensive isolation wards of a designated hospital of a province from January to April 2020 were analyzed retrospectively, patients complicated with MDRO infection were selected as case group and those without MDR infection were as control group. Clinical data of two groups of patients were compared, risk factors for critical COVID-19 complicated with MDRO infection were conducted multivariate logistic regression analysis. Results There were 62 cases of critical patients with COVID-19. 10 of whom were complicated with MDRO infection, and 52 cases were not complicated with MDRO infection, 14 patients (22.6%) were complicated with bacterial or fungal infection; 10 patients (16.1%) were complicated with MDRO infection, including 4 cases of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection and 6 cases of carbapenem-resistant Acine-tobacter baumannii (CRAB) infection; 9 cases (11 strains) were complicated with non-MDRO or fungal infection. Univariate analysis showed that the proportion of central venous catheterization, the types of used antimicrobial agents, and proportion of antimicrobial use ≥ 4 types in case group were all higher than those in control group; albumin level in case group was lower than control group; differences were all statistically significant (all P < 0.05). Multivariate analysis showed that independent risk factors for critical COVID-19 patients complicated with MDRO infection were the use of ≥ 4 types of antimicrobial agents (OR=17.104, 95%CI: 1.805-162.033), while albumin was the protective factor (OR=0.834, 95%CI: 0.709-0.982). Conclusion Critical COVID-19 patients should use antimicrobial agents rationally and elevate the level of albumin, which is conducive to the prevention and control of critical COVID-19 complicated with MDRO infection.